The invention relates, in part, to amine cationic lipid compounds, as well as formulations thereof, and their use in the delivery of therapeutic agents, such as nucleic acid molecules, to cells.
Nucleic acid molecules cannot easily cross cell membranes because of their size and hydrophilicity. Delivery has therefore been one of the major challenges for nucleic acid therapeutics, e.g., antisense payloads and RNAi technology. To trigger RNase H activity or RNAi activity following systemic administration, a formulation containing nucleic acid molecules not only must (1) protect the payload from enzymatic and non-enzymatic degradation and (2) provide appropriate biodistribution of the formulation, but also (3) allow cellular uptake or internalization of the formulation and (4) facilitate delivery of the nucleic acid payload to the cytoplasm of the cell. Many formulations that excel in criteria 1 and 2 above are deficient in criteria 3 and 4, and many nucleic acid formulations therefore show excellent biodistribution but fail to knock down the target gene due to lack of systemic delivery and local delivery.
Accordingly, there is a need for new compounds for the delivery of therapeutic agents, such as RNAi agents. In particular, compounds capable of acting as cationic lipids may be used in lipid particle formulations to deliver nucleic acid payloads to cells.